Perfluorocarbon-Encapsulated Porphyrin-Lipid Nanoparticles as a Photoactive Pyroptosis Inducer for Cancer Therapy

Abstract

Pyroptosis is a unique mode of programmed cell death extensively accepted to outperform apoptosis in inducing rapid cell death and evoking potent immune responses for further inhibiting tumor progression, recurrence, and metastasis. Therefore, developing a safe and efficient pyroptosis inducer of cancer cells is highly desired. In this study, a biocompatible amphiphilic tetraphenylporphyrin–lysophospholipid conjugate (PPNH2-PC) was synthesized and further self-assembled with perfluorooctyl bromide (PFOB), forming PFOB-encapsulated porphyrin–lipid nanoparticles (PFOB@PPNH2-PC NPs) with a narrow size distribution of about 64.1 nm. Compared with the PPNH2-PC NPs without PFOB, the PFOB@PPNH2-PC NPs exhibited higher reactive oxygen species (ROS)-generating capability under light irradiation and induced more cellular death. We found that PFOB@PPNH2-PC NPs induced approximately 12 times more pyroptosis bubbles than PPNH2-PC NPs after 5-min light irradiation. Further analysis showed that pyroptosis was induced via caspase 3–mediated gasdermin E cleavage. Hence, this PFOB-encapsulated lipid NP holds the potential for further development as a photoactivatable pyroptosis inducer for cancer therapy.